scholarly journals Tumor-associated immune cell infiltrate density in penile squamous cell carcinomas

2022 ◽  
Author(s):  
Luca Hladek ◽  
Katrin Bankov ◽  
Jens von der Grün ◽  
Natalie Filmann ◽  
Melanie Demes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell ◽  
Survival Data ◽  
Immune Cell ◽  
Tumor Biology ◽  
Squamous Cell Carcinomas ◽  
Cell Infiltrate ◽  
Advanced Tumor ◽  
Tumor Stages ◽  
Immune Cell Infiltrate

AbstractPenile squamous cell carcinomas are rare tumor entities throughout Europe. Early lymphonodal spread urges for aggressive therapeutic approaches in advanced tumor stages. Therefore, understanding tumor biology and its microenvironment and correlation with known survival data is of substantial interest in order to establish treatment strategies adapted to the individual patient. Fifty-five therapy naïve squamous cell carcinomas, age range between 41 and 85 years with known clinicopathological data, were investigated with the use of tissue microarrays (TMA) regarding the tumor-associated immune cell infiltrate density (ICID). Slides were stained with antibodies against CD3, CD8 and CD20. An image analysis software was applied for evaluation. Data were correlated with clinicopathological characteristics and overall survival. There was a significant increase of ICID in squamous cell carcinomas of the penis in relation to tumor adjacent physiological tissue. Higher CD3-positive ICID was significantly associated with lower tumor stage in our cohort. The ICID was not associated with overall survival. Our data sharpens the view on tumor-associated immune cell infiltrate in penile squamous cell carcinomas with an unbiased digital and automated cell count. Further investigations on the immune cell infiltrate and its prognostic and possible therapeutic impact are needed.

Immune cell infiltrate differences in pilocytic astrocytoma and glioblastoma: evidence of distinct immunological microenvironments that reflect tumor biology

2011 ◽  
Vol 115 (3) ◽  
pp. 505-511 ◽  
Author(s):  
Isaac Yang ◽  
Seunggu J. Han ◽  
Michael E. Sughrue ◽  
Tarik Tihan ◽  
Andrew T. Parsa
Keyword(s):  
Pilocytic Astrocytoma ◽  
Immune Cell ◽  
Tumor Biology ◽  
Human Leukocyte ◽  
Low Grade ◽  
High Grade ◽  
Cell Infiltrate ◽  
Leukocyte Antigen ◽  
Pilocytic Astrocytomas ◽  
Immune Cell Infiltrate

Object The tumor microenvironment in astrocytomas is composed of a variety of cell types, including infiltrative inflammatory cells that are dynamic in nature, potentially reflecting tumor biology. In this paper the authors demonstrate that characterization of the intratumoral inflammatory infiltrate can distinguish high-grade glioblastoma from low-grade pilocytic astrocytoma. Methods Tumor specimens from ninety-one patients with either glioblastoma or pilocytic astrocytoma were analyzed at the University of California, San Francisco. A systematic neuropathology analysis was performed. All tissue was collected at the time of the initial surgery prior to adjuvant treatment. Immune cell infiltrate not associated with necrosis or hemorrhage was analyzed on serial 4-μm sections. Analysis was performed for 10 consecutive hpfs and in 3 separate regions (total 30 × 0.237 mm2). Using immunohistochemistry for markers of infiltrating cytotoxic T cells (CD8), natural killer cells (CD56), and macrophages (CD68), the inflammatory infiltrates in these tumors were graded quantitatively and classified based on microanatomical location (perivascular vs intratumoral). Control markers included CD3, CD20, and human leukocyte antigen. Results Glioblastomas exhibited significantly higher perivascular (CD8) T-cell infiltration than pilocytic astrocytomas (62% vs 29%, p = 0.0005). Perivascular (49%) and intratumoral (89%; p = 0.004) CD56-positive cells were more commonly associated with glioblastoma. The CD68-positive cells also were more prevalent in the perivascular and intratumoral space in glioblastoma. In the intratumoral space, all glioblastomas exhibited CD68-positive cells compared with 86% of pilocytic astrocytomas (p = 0.0014). Perivascularly, CD68-positive infiltrate was also more prevalent in glioblastoma when compared with pilocytic astrocytoma (97% vs 86%, respectively; p = 0.0003). The CD3-positive, CD20-positive, and human leukocyte antigen-positive infiltrates did not differ between glioblastoma and pilocytic astrocytoma. Conclusions This analysis suggests a significantly distinct immune profile in the microenvironment of high-grade glioblastoma versus low-grade pilocytic astrocytoma. This difference in tumor microenvironment may reflect an important difference in the tumor biology of glioblastoma.

scholarly journals The peri- and intratumoral immune cell infiltrate and PD-L1 status in invasive squamous cell carcinomas of the penis

2021 ◽  
Author(s):  
T. Müller ◽  
M. Demes ◽  
A. Lehn ◽  
J. Köllermann ◽  
S. Vallo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Hpv Infection ◽  
Tumor Type ◽  
Cell Infiltrate ◽  
Immune Cell Infiltrate ◽  
Checkpoint Inhibitor Therapy ◽  
Invasive Carcinomas ◽  
Immune Cell Score

Abstract Introduction Penile carcinomas are rare tumors throughout Europe. Therefore, little attention is drawn to this disease. That makes it important to study tumor-associated key metrics and relate these to known data on penile neoplasias. Materials and methods A cohort of 60 well-defined penile invasive carcinomas with known human papillomavirus (HPV) infection status was investigated. Data on tumor type, grading and staging were recorded. Additionally, data on the peri- and intratumoral immune cell infiltrate in a semiquanititave manner applying an HE stain were assessed. Results Our study showed a significant correlation of immune cell infiltrate and pT stage with overall survival. Therefore, in a subset of tumors, PD-L1 staining was applied. For tumor proportion score (TPS), 26 of 30 samples (87%) were scored >0%. For the immune cell score (IC), 28 of 30 samples (93%) were defined as >0% and for CPS, 29 of 30 samples (97%) scored >0. PD-L1 expression was not associated with overall survival. Conclusion PD-L1 is expressed in penile carcinomas, providing a rationale for targeted therapy with checkpoint inhibitors. We were able to show that immune reaction appears to be prognostically relevant. These data enhance the need for further studies on the immune cell infiltrate in penile neoplasias and show that PD-L1 expression is existent in our cohort, which may be a potential target for checkpoint inhibitor therapy.

scholarly journals No Association of the NF-κB1 −94INS/Delattg Promoter Polymorphism with Relapse-Free and Overall Survival in Patients with Squamous Cell Carcinomas of the Head and Neck Region

2008 ◽  
Vol 21 (4) ◽  
pp. 827-832 ◽  
Author(s):  
G.F. Lehnerdt ◽  
A. Bankfalvi ◽  
S. Grehl ◽  
M. Adamzik ◽  
S. Lang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Region ◽  
Promoter Polymorphism ◽  
Squamous Cell Carcinomas ◽  
Prognostic Impact ◽  
Curative Intent ◽  
Head And Neck Region ◽  
Tumor Stages

The transcription factor, nuclear factor-κB (NF-κB) is known to play a major role in immune response, inflammation and, via apoptosis and proliferation, also in oncogenesis. Transcription of NFKB1, which encodes the subunit p50/p105 of NF-κB, seems to be influenced by an insertion/deletion polymorphism in its promoter region. Accordingly, the goal of this study is to investigate whether this polymorphism can serve as a putative prognostic marker in patients with Squamous Cell Carcinomas of the Head and Neck region (HNSCC). The prognostic value of the −94ins/delATTG NFKB1 promoter polymorphism was analyzed in an unselected series of patients treated with curative intent for HNSCC, including all tumor stages with different therapeutical regimens. Genotyping was performed by means of pyrosequencing, using DNA from paraffin-embedded tissue samples from 364 patients with a median follow-up of 61 (2-143) months. The various genotypes were correlated with relapse-free and overall survival, as well as risk, compared to healthy volunteers. The NFKB1 polymorphism was not related to risk of HNSCC. Kaplan-Meier curves revealed no significant association between the −94ins/delATTG alleles and survival or disease progression of patients with HNSCC. In conclusion, the results suggest that the investigated NFKB1 promoter polymorphism has no prognostic impact on risk or clinical course in HNSCC.

scholarly journals Distribution of tumor-infiltrating-T-lymphocytes and possible tumor-escape mechanisms avoiding immune cell attack in locally advanced adenocarcinomas of the esophagus

2021 ◽  
Author(s):  
M. Schoemmel ◽  
◽  
H. Loeser ◽  
M. Kraemer ◽  
S. Wagener-Ryczek ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Cell ◽  
Locally Advanced ◽  
Tumor Escape ◽  
Inflammatory Microenvironment ◽  
Advanced Tumor ◽  
Tumor Stages ◽  
Tumor Center ◽  
Class 1

Abstract Introduction The inflammatory microenvironment has emerged as one of the focuses of cancer research. Little is known about the immune environment in esophageal adenocarcinoma (EAC) and possible tumor-escape mechanisms to avoid immune cell attack. Patients and methods We measured T cell inflammation (CD3, CD8) in the microenvironment using a standardized software-based evaluation algorithm considering different predefined tumor areas as well as expression of MHC class 1 and PD-L1 on 75 analyzable primarily resected and locally advanced (≥ pT2) EACs. We correlated these findings statistically with clinical data. Results Patients with high amounts of T cell infiltration in their tumor center showed a significant survival benefit of 41.4 months compared to 16.3 months in T cell poor tumors (p = 0.025), although CD3 fails to serve as an independent prognostic marker in multivariate analysis. For the invasion zone, a correlation between number of T-cells and overall survival was not detectable. Loss of MHC1 protein expression on tumor cells was seen in 32% and PD-L1 expression using the combined positive score (CPS) in 21.2%. Most likely due to small numbers of cases, both markers are not prognostically relevant, even though PD-L1 expression correlates with advanced tumor stages. Discussion Our analyses reveal an outstanding, though not statistically independent, prognostic relevance of T-cell-rich inflammation in our group of EACs, in particular driven by the tumor center. For the first time, we describe that the inner part of the invasion zone in EACs shows significantly fewer T-cells than other tumor segments and is prognostically irrelevant. We also demonstrate that the loss of antigen presenting ability via MHC1 downregulation by the carcinoma cells is a common escape mechanism in EACs. Future work will need to show whether tumors with MHC class 1 loss respond less well to immunotherapy.

scholarly journals Signaling pathways and immune evasion mechanisms in classical Hodgkin lymphoma

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 310-316 ◽  
Author(s):  
W. Robert Liu ◽  
Margaret A. Shipp
Keyword(s):  
Hodgkin Lymphoma ◽  
Immune Evasion ◽  
Copy Number ◽  
Genetic Basis ◽  
Immune Cell ◽  
Classical Hodgkin Lymphoma ◽  
Copy Number Alterations ◽  
Cell Infiltrate ◽  
Immune Cell Infiltrate ◽  
Survival And Growth

Abstract Classical Hodgkin lymphoma (cHL) is an unusual B-cell–derived malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an extensive but ineffective inflammatory/immune cell infiltrate. This striking feature suggests that malignant HRS cells escape immunosurveillance and interact with immune cells in the cancer microenvironment for survival and growth. We previously found that cHLs have a genetic basis for immune evasion: near-uniform copy number alterations of chromosome 9p24.1 and the associated PD-1 ligand loci, CD274/PD-L1 and PDCD1LG2/PD-L2, and copy number–dependent increased expression of these ligands. HRS cells expressing PD-1 ligands are thought to engage PD-1 receptor–positive immune effectors in the tumor microenvironment and induce PD-1 signaling and associated immune evasion. The genetic bases of enhanced PD-1 signaling in cHL make these tumors uniquely sensitive to PD-1 blockade.

scholarly journals Expression and clinical significance of the receptors of the EGF family in oral squamous cell carcinomas

2019 ◽  
Vol 4 ◽  
pp. 2057178X1983653
Author(s):  
Upul Dissanayake
Keyword(s):  
Overall Survival ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Growth Factor ◽  
Squamous Cell ◽  
Logistic Regression Analysis ◽  
Growth Factor Receptor ◽  
Squamous Cell Carcinomas ◽  
Her 2

Objective: To examine the immunohistochemical expression of four members of the type 1 growth factor receptor family in oral squamous cell carcinomas (OSCCs) and to correlate with clinical outcomes. Materials and methods: Sixty OSCCs from a patient cohort in Sri Lanka were included in the study. Five sections from each carcinoma were immunostained with antibodies to epidermal growth factor receptor (EGFR)/c-erbB-1, c-erbB-2/HER-2/neu, c-erbB-3/HER-3 and c-erbB-4/HER-4. Two clones were used to stain for c-erbB-2/HER-2/neu. Semiquantitative analysis of immunoreactivity was carried out by scoring the intensity of expression and proportions of positively stained cells. A logistic regression analysis was performed to examine positive expression against overall survival. Results: There was heterogenous expression of the four receptors, positivity ranging from 26% to 60%. Co-expression of all four markers was observed only in 1–3% of the tumours. Both membranous and cytoplasmic expressions were observed, EGFR showing predominantly membranous expression and c-erbB-2 showing only cytoplasmic staining. In logistic regression analysis, none of the growth factor receptors were significantly predictive of overall survival. Conclusion: Type 1 growth factor receptors are highly expressed in oral carcinomas, EGFR being the predominant marker.

scholarly journals Immune Cell Infiltrate in Chronic-Active Antibody-Mediated Rejection

2020 ◽  
Vol 10 ◽  
Author(s):  
Kasia A. Sablik ◽  
Ekaterina S. Jordanova ◽  
Noelle Pocorni ◽  
Marian C. Clahsen-van Groningen ◽  
Michiel G. H. Betjes
Keyword(s):  
Immune Cell ◽  
Cell Infiltrate ◽  
Antibody Mediated Rejection ◽  
Immune Cell Infiltrate
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